Hubei Province Engineering Research Center of Healthy Food, School of Biology and Pharmaceutical Engineering, Wuhan Polytechnic University, Wuhan 430023, China.
Department of Anesthesiology, Washington University in St. Louis, St. Louis, MO, 63110, USA.
J Nutr Biochem. 2021 Feb;88:108481. doi: 10.1016/j.jnutbio.2020.108481. Epub 2020 Aug 25.
Excessive consumption of saturated fat leads to non-alcoholic fatty liver disease (NAFLD), which is attenuated by supplementation of n-3 polyunsaturated fatty acids (PUFAs). Endoplasmic reticulum (ER) stress is crucial in the development of NAFLD, but how high-saturated fat diet (HFD) causes ER stress and NAFLD remains unclear. Lectin-like oxidized low-density lipoprotein receptor-1 (LOX-1) is involved in hepatic ER stress. We aimed to explore the roles of LOX-1 in HFD-induced ER stress. Male Sprague-Dawley rats were fed an HFD without or with supplementation of fish oil for 16 weeks. The effects of n-3 PUFAs on hepatic ER stress degrees and the expression levels of LOX-1 were examined. Then human L02 hepatoma cells were treated with palmitate or palmitate and DHA to determine the ER stress and LOX-1 expression levels in vitro. After that the expression of LOX-1 in L02 cells was either knocked-down or overexpressed to analyze the roles of LOX-1 in palmitate-induced ER stress. The feeding of HFD induced NAFLD development and ER stress in the liver, and LOX-1 expressing level, which were all reversed by fish oil supplementation. In vitro, DHA treatment reduced the expression of LOX-1, and palmitate-induced ER stress. SiRNA-mediated knock-down of LOX-1 inhibited palmitate-induced ER stress, whereas overexpression of LOX-1 dramatically induced ER stress in L02 cells.LOX-1 is critical for HFD-induced ER stress, and inhibition of its expression under the treatment of n-3 PUFAs could ameliorate HFD-induced NAFLD.
过量摄入饱和脂肪可导致非酒精性脂肪性肝病（NAFLD），而 n-3 多不饱和脂肪酸（PUFAs）的补充可减轻其病情。内质网（ER）应激在 NAFLD 的发生发展中起着至关重要的作用，但高饱和脂肪饮食（HFD）如何导致 ER 应激和 NAFLD 尚不清楚。凝集素样氧化型低密度脂蛋白受体-1（LOX-1）参与肝脏 ER 应激。本研究旨在探讨 LOX-1 在 HFD 诱导的 ER 应激中的作用。雄性 Sprague-Dawley 大鼠喂食 HFD 或 HFD 补充鱼油 16 周。检测 n-3 PUFAs 对肝 ER 应激程度和 LOX-1 表达水平的影响。然后用人 L02 肝癌细胞用棕榈酸或棕榈酸和 DHA 处理，以确定体外 ER 应激和 LOX-1 表达水平。之后敲低或过表达 L02 细胞中的 LOX-1，以分析 LOX-1 在棕榈酸诱导的 ER 应激中的作用。HFD 喂养诱导 NAFLD 发展和肝脏 ER 应激，而 LOX-1 表达水平可被鱼油补充所逆转。体外，DHA 处理可降低 LOX-1 的表达，并减轻棕榈酸诱导的 ER 应激。LOX-1 的 siRNA 介导敲低可抑制棕榈酸诱导的 ER 应激，而过表达 LOX-1 可显著诱导 L02 细胞的 ER 应激。LOX-1 对 HFD 诱导的 ER 应激至关重要，n-3 PUFAs 处理抑制其表达可改善 HFD 诱导的 NAFLD。
